Biodistribution of phosphodiester and phosphorothioate siRNA

Intratumor RNA interference of cell cycle genes slows down tumor progression

“…In fact, the half-life of unmodified siRNAs is short, especially in vivo, due to rapid elimination by the kidney and rapid degradation by serum RNases, with a half-life of o10 min. 9 The stability of siRNA has been significantly increased by chemical conjugation or modifications of the sugar backbone and by capping the ends of the siRNA. Chemical modifications at the 2¢ position of the ribose, introduction of 2¢-F pyrimidines, deoxy purines and inverted deoxy abasic end cap in the sense strand as well as 2¢-F pyrimidines and 2¢-OMe purines in the antisense strand and incorporation of the 3¢-S-phosphorothioate modification into the strands of RNA led to half-life in the range of hours.…”

“…17 Therefore, the use of RNAi by a stable viral vector system, such as the adenovirus (Ad), is a possible strategy for stable gene knockdown. In fact, constitutive expression of short hairpin RNA by Ad vectors has been shown for several weeks, thereby consolidating this technology as an alternative to generating liver-specific knockout animals, 18 as development of potential agents to treat hepatitis B 9,19,20 or to generate antitumor therapies against antiapoptotic genes 18,21 or genes involved in the cell cycle. 22 The objective of this study was to achieve intratumoral local delivery of siRNA using LNPs or Ad vectors.…”

Reconstituted influenza virus envelopes as an efficient carrier system for cellular delivery of small-interfering RNAs

“…Moreover, free siRNA is considered to be vulnerable to degradation under in vivo conditions. 19,20 Attempts to improve delivery of siRNA in vivo include complexation of siRNA to polyethylenimine, formulation of siRNA with cationic lipids or collagen derivatives, and entrapment of siRNA in biodegradable microspheres. 19,[21][22][23][24][25] Most of these approaches aim primarily at improving the protection of siRNA from degradation and prolonging the circulation time.…”

Structure - Functions Relations in Small Interfering RNAs

“…5 min) siRNA elimination from organism resulted from its hydrophobicity and size of the molecule (approx. 14 kDa) [56,57], ii) high nuclease sensitivity of siRNA [58,59,60,61,62] and iii) inefficient or/and non-specific delivery into target cells [63]. Intracellular factors are related to RISC assembly and the efficiency of binding to and cleaving the target.…”